FMT safe, linked to reduced hepatic encephalopathy recurrence in patients with cirrhosis
Key takeaways:
- FMT demonstrated a favorable safety profile with no related adverse or serious adverse events.
- Hepatic encephalopathy rates were similar regardless of oral or enema route, number of doses or donor type.
Fecal microbiota transplant, regardless of dose or route, was safe and associated with reduced hepatic encephalopathy recurrence among patients with cirrhosis receiving lactulose and rifaximin, according to a study in Journal of Hepatology.
“FMT to beneficially alter the gut-liver-brain axis in hepatic encephalopathy has been performed safely in prior smaller studies using enema or capsule routes with promising results,” Jasmohan S. Bajaj, MD, MS, FACG, professor in the division of gastroenterology, hepatology and nutrition at Virginia Commonwealth University, and colleagues wrote. “However, important questions remain regarding route, dosing and impact on clinical outcomes that require larger studies with standardized products.”
To determine the impact of different FMT doses, routes and donor types on safety and hepatic encephalopathy recurrence, Bajaj and colleagues conducted a double-blind, placebo-controlled, randomized phase 2 clinical trial of 60 patients aged 21 years or older with cirrhosis treated with lactulose and rifaximin (Xifaxan, Salix Pharmaceuticals).
All patients received two capsules and one enema, randomly assigned to active enema and capsules at baseline and day 30 (group 1, n = 15), placebo enema and active capsules at baseline and day 30 (group 2, n = 15), active enema at baseline and placebo capsules at both timepoints (group 3, n = 15) or placebo enema and capsules (group 4, n = 15).
The primary outcome was occurrence of adverse or serious adverse events related to FMT within 6 months of enrollment. Secondary outcomes included hepatic encephalopathy recurrence, all-cause hospitalizations, death, donor engraftment and quality of life.
Of the two donors used for engraftment, one was vegan and the other omnivorous.
The researchers observed that there were no FMT-related adverse or serious adverse events among any of the groups that received FMT.
Ten patients (17%) experienced hepatic encephalopathy recurrence, with a significant difference in incidence between groups (P = .035). Specifically, a post-hoc analysis revealed that recurrence was significantly higher in the all-placebo group vs. any of the FMT groups (40% vs. 9.1%), with an OR of 0.15 (95% CI, 0.04-0.64).
Among the groups that received FMT, there were no significant differences in hepatic encephalopathy recurrence related to route or dose, according to the researchers.
Additionally, there were improvements in physical and psychosocial aspects of quality of life in groups 1 and 2.
Although baseline microbial diversity did not appear to predict recurrence, the researchers noted that patients who developed hepatic encephalopathy recurrence were more likely to have lower Lachnospiraceae and higher Lactobacillaceae. They also noted that FMT donor engraftment was highest among patients with greater levels of Lachnospiraceae before FMT, with the highest engraftment rates overall seen in group 1.
“Patients with hepatic encephalopathy on lactulose and rifaximin are an underserved population with a large medical, psychosocial and financial burden,” the researchers wrote. “Interventions that reduce their risk of recurrence are critical since these patients are often not prioritized for liver transplantation. Our experience, which is the largest cohort of such patients to date, showing safety of FMT products regardless of route or dose is encouraging.”
Bajaj and colleagues acknowledged several study limitations, including its relatively small sample size and restrictive eligibility criteria.
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